Drug class: Reversible COX-1/COX-2 Inhibitors

Medically reviewed by Drugs.com on Aug 10, 2025. Written by ASHP.

Introduction

Prototypical NSAIA;^{1 2 3 6 7} propionic acid derivative.⁷

Uses for Flurbiprofen

Inflammatory Diseases

Symptomatic treatment of rheumatoid arthritis and osteoarthritis.^{1 2 3 4 5 6 7 10}

Guidelines from the American College of Rheumatology (ACR) for treatment of rheumatoid arthritis recommend initiation of a disease-modifying antirheumatic drug (DMARD) for most patients; role of NSAIAs not discussed.²⁰⁰¹

ACR recommends topical/oral NSAIAs for treatment of osteoarthritis, among other interventions.²⁰⁰² Therapy selection is patient-specific; factors to consider include patients' values and preferences, risk factors for serious adverse GI effects, existing comorbidities (e.g., hypertension, heart failure, other cardiovascular disease, chronic kidney disease), injuries, disease severity, surgical history, and access to and availability of interventions.²⁰⁰²

NSAIAs have also been used in other inflammatory diseases includingankylosing spondylitis^{† [off-label]} , gout^{† [off-label]}, and psoriatic arthritis^{† [off-label]}.^{2 6 8 24 25}

Flurbiprofen Dosage and Administration

General

Pretreatment Screening

• Correct volume status in dehydrated or hypovolemic patients before initiating flurbiprofen therapy.¹

Patient Monitoring

• Monitor renal function during flurbiprofen therapy in patients with renal or hepatic impairment, heart failure, dehydration, or hypovolemia.¹

• Monitor BP closely during initiation and throughout NSAIA therapy.¹

• Monitor patients with certain coexisting conditions such as coagulation disorders and those receiving concomitant therapy with anticoagulants, antiplatelet agents, selective serotonin-reuptake inhibitors (SSRIs), and serotonin norepinephrine reuptake inhibitors (SNRIs) for signs of bleeding.¹

• Consider monitoring CBC and chemistry profile periodically during long-term therapy.¹

• Monitor hemoglobin or hematocrit in patients with any signs or symptoms of anemia.¹

• Monitor for GI ulceration and bleeding; even closer GI monitoring is recommended in those receiving concomitant low-dose aspirin for cardiac prophylaxis.¹

• In patients with asthma but without known aspirin sensitivity, monitor for changes in signs and symptoms of asthma.¹

• Monitor for symptoms of cardiovascular thrombotic events, including chest pain, shortness of breath, weakness, or slurred speech.¹ If flurbiprofen is used in patients with severe heart failure, monitor patients for signs of worsening heart failure.¹

Dispensing and Administration Precautions

• The 2023 American Geriatrics Society (AGS) Beers Criteria for Potentially Inappropriate Medication (PIM) Use in Older Adults includes flurbiprofen on the list of PIMs that are best avoided by older adults in most circumstances or under specific situations, such as certain diseases, conditions, or care settings.⁹⁹⁹ The criteria are intended to apply to adults 65 years of age and older in all ambulatory, acute, and institutional settings of care, except hospice and end-of-life care settings.⁹⁹⁹ For non-COX-2-selective oral NSAIAs such as flurbiprofen, the Beers Criteria Expert Panel specifically recommends that chronic use be avoided unless other alternatives are not effective and the patient can take a gastroprotective agent (proton-pump inhibitor or misoprostol).⁹⁹⁹ Additionally, short-term scheduled use should be avoided in combination with oral or parenteral corticosteroids, anticoagulants, or antiplatelet agents unless other alternatives are not effective and the patient can take a gastroprotective agent.⁹⁹⁹

Other General Considerations

• Use NSAIAs with caution and careful monitoring (e.g., monitor for development of cardiovascular events throughout therapy, even in those without prior cardiovascular symptoms) and at the lowest effective dosage for the shortest duration necessary.¹

• Avoid use of more than one NSAIA at a time.¹

• Avoid use in patients with recent MI unless the benefits of therapy are expected to outweigh the risks of recurrent cardiovascular thrombotic events; if flurbiprofen is used in such patients, the patient should be monitored for cardiac ischemia.¹

• Avoid use in patients with severe heart failure unless benefits of therapy are expected to outweigh risks of worsening heart failure; if used, monitor for worsening heart failure.¹

Administration

Oral Administration

Administer orally 2–4 times daily.^{1 13 14}

Administration with food or antacids may alter rate but not extent of absorption.^{1 13 26}

Dosage

Adjust dosage based on individual requirements and response; attempt to titrate to the lowest effective dosage.¹

Adults

Inflammatory Diseases

Osteoarthritis or Rheumatoid Arthritis

Oral

200–300 mg daily given in 2–4 divided doses.^{1 3} Maximum 100 mg in a single dose.¹ Similar efficacy whether the total daily dosage of flurbiprofen is administered in 2, 3, or 4 divided doses.^{2 9}

Special Populations

Hepatic Impairment

Dosage reduction may be necessary.^{1 3 15}

Renal Impairment

Mild renal impairment: Dosage adjustment not required.¹

Moderate or severe renal impairment: Dosage reduction may be necessary.¹

Geriatric Patients

Use with caution and at the lowest effective dosage for the shortest possible duration.¹

Pharmacogenomic Considerations in Dosing

CYP2C9 poor metabolizers: Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines recommend initiating flurbiprofen at a dosage that is 25–50% of the lowest recommended initial dosage and cautiously titrating according to clinical effect up to a dosage that is 25–50% of the maximum recommended dosage.⁵²⁰ Do not increase dosage until steady-state concentrations are attained (≥5 days after initial dose).⁵²⁰ Alternatively, consider a drug that is not metabolized by CYP2C9 or is not substantially affected by CYP2C9 genetic variants in vivo.⁵²⁰

CYP2C9 intermediate metabolizers with a diplotype functional activity score (AS) of 1: CPIC guidelines recommend initiating flurbiprofen at the lowest recommended initial dosage and cautiously titrating according to clinical effect up to the maximum recommended dosage.⁵²⁰

Intermediate metabolizers with an AS of 1.5: May receive dosages recommended for normal metabolizers.⁵²⁰

Cautions for Flurbiprofen

Contraindications

• Known hypersensitivity to flurbiprofen or any ingredient in the formulation.¹

• History of asthma, urticaria, or other sensitivity reactions precipitated by aspirin or other NSAIAs.¹

• In the setting of CABG surgery.¹

Warnings/Precautions

Warnings

Cardiovascular Effects

NSAIAs (selective COX-2 inhibitors, prototypical NSAIAs) increase the risk of serious adverse cardiovascular thrombotic events (e.g., MI, stroke) in patients with or without cardiovascular disease or risk factors for cardiovascular disease (see Boxed Warning).¹

Relative increase in risk appears to be similar in patients with or without known underlying cardiovascular disease or risk factors for cardiovascular disease, but the absolute incidence of serious NSAIA-associated cardiovascular thrombotic events is higher in those with cardiovascular disease or risk factors for cardiovascular disease because of their elevated baseline risk.⁵⁰⁶

Increased risk may occur early (within the first weeks) following initiation of therapy and may increase with higher dosages and longer durations of use.^{505 506}

In controlled studies, increased risk of MI and stroke observed in patients receiving a selective COX-2 inhibitor for analgesia in first 10–14 days following CABG surgery.¹

In patients receiving NSAIAs following MI, increased risk of reinfarction and death observed beginning in the first week of treatment.⁵⁰⁵

Increased 1-year mortality rate observed in patients receiving NSAIAs following MI; absolute mortality rate declined somewhat after the first post-MI year, but the increased relative risk of death persisted over at least the next 4 years.⁵¹¹

Use NSAIAs with caution and careful monitoring (e.g., monitor for development of cardiovascular events throughout therapy, even in those without prior cardiovascular symptoms) and at the lowest effective dosage for the shortest duration necessary.¹

Avoid use in patients with recent MI unless benefits of therapy are expected to outweigh risks of recurrent cardiovascular thrombotic events; if used, monitor for cardiac ischemia.¹ Contraindicated in the setting of CABG surgery.¹

Monitor for possible development of cardiovascular thrombotic events throughout therapy.¹

No consistent evidence that concomitant use of low-dose aspirin mitigates the increased risk of serious adverse cardiovascular events associated with NSAIAs.¹

GI Effects

Serious, sometimes fatal, GI toxicity (e.g., bleeding, ulceration, perforation) can occur with or without warning symptoms.^{1 15 27}

Risk for GI bleeding increased more than 10-fold in patients with a history of peptic ulcer disease and/or GI bleeding who are receiving NSAIAs compared with patients without these risk factors.¹

Other risk factors for GI bleeding include concomitant use of oral corticosteroids, anticoagulants, aspirin, or SSRIs; longer duration of NSAIA therapy (however, short-term therapy is not without risk); smoking; alcohol use; older age; poor general health status; and advanced liver disease and/or coagulopathy.¹

Most spontaneous reports of fatal adverse GI effects involve geriatric or debilitated patients.¹

Frequency of NSAIA-associated upper GI ulcers, gross bleeding, or perforation is approximately 1% in patients receiving NSAIAs for 3–6 months and 2–4% at one year.¹

Use lowest effective dosage for the shortest duration necessary.¹

Avoid use of more than one NSAIA at a time.¹

Avoid use of NSAIAs in patients at higher risk for GI toxicity unless expected benefits outweigh increased risks of bleeding; consider alternate therapies in high-risk patients and those with active GI bleeding.¹

Monitor for GI ulceration and bleeding; closer monitoring for GI bleeding recommended in those receiving concomitant low-dose aspirin for cardiac prophylaxis.¹

If serious adverse GI event suspected, promptly initiate evaluation and discontinue therapy until serious adverse GI event ruled out.¹

Other Warnings and Precautions

Hepatotoxicity

Severe (sometimes fatal) reactions including jaundice, fulminant hepatitis, liver necrosis, and hepatic failure reported rarely with NSAIAs.¹

Elevations of serum ALT or AST reported.¹

Monitor for symptoms and/or signs suggesting liver dysfunction.¹ Discontinue immediately and perform clinical evaluation if signs or symptoms of liver disease or systemic manifestations (e.g., eosinophilia, rash) occur.¹

Hypertension

Hypertension and worsening of preexisting hypertension reported; either event may contribute to the increased incidence of cardiovascular events.¹ Monitor BP during initiation of flurbiprofen and throughout therapy.¹

Heart Failure and Edema

Fluid retention and edema reported.¹

NSAIAs (selective COX-2 inhibitors, prototypical NSAIAs) may increase morbidity and mortality in patients with heart failure. ^{501 504}

NSAIAs may diminish cardiovascular effects of diuretics, ACE inhibitors, or angiotensin II receptor antagonists used to treat heart failure or edema.¹

Manufacturer recommends avoiding use in patients with severe heart failure unless benefits of therapy are expected to outweigh risks of worsening heart failure; if used, monitor for worsening heart failure.¹

Renal Toxicity and Hyperkalemia

Direct renal injury, including renal papillary necrosis, reported in patients receiving long-term NSAIA therapy.¹

Potential for overt renal decompensation.¹ Increased risk of renal toxicity in patients with renal or hepatic impairment or heart failure, in geriatric patients, in patients with volume depletion, and in those receiving a diuretic, ACE inhibitor, or angiotensin II receptor antagonist.¹

Correct dehydration before initiating flurbiprofen therapy; monitor renal function during therapy in patients with renal or hepatic impairment, heart failure, dehydration, or hypovolemia.¹

Hyperkalemia reported with NSAIAs, even in some patients without renal impairment; in such patients, effects attributed to a hyporeninemic-hypoaldosteronism state.¹

Anaphylactic Reactions

Anaphylactic reactions reported.¹ Seek immediate medical intervention and discontinue drug for anaphylaxis.¹

Exacerbation of Asthma Related to Aspirin Sensitivity

Monitor for changes in manifestations of asthma; use is contraindicated in patients with aspirin-sensitive asthma.¹

Serious Skin Reactions

Serious skin reactions (e.g., exfoliative dermatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis) reported; can occur without warning.¹

Discontinue at first appearance of rash or any other sign of hypersensitivity (e.g., blisters, fever, pruritus).¹

Drug Reaction with Eosinophilia and Systemic Symptoms

Drug reaction with eosinophilia and systemic symptoms (DRESS), a potentially fatal or life-threatening syndrome, reported in patients receiving NSAIAs.¹ Typically presents with fever, rash, lymphadenopathy, and/or facial swelling; other clinical manifestations may include hepatitis, nephritis, hematologic abnormalities, myocarditis, myositis.¹ Symptoms may resemble those of acute viral infection.¹ Eosinophilia is often present.¹

Clinical presentation is variable, and other organ systems may be involved.¹

Early manifestations of hypersensitivity (e.g., fever, lymphadenopathy) may be present in the absence of rash.¹

If signs or symptoms of DRESS develop, discontinue flurbiprofen and immediately evaluate patient.¹

Fetal/Neonatal Morbidity and Mortality

Use of NSAIAs during pregnancy at about ≥30 weeks’ gestation can cause premature closure of the fetal ductus arteriosus; use at about ≥20 weeks’ gestation associated with fetal renal dysfunction resulting in oligohydramnios and, in some cases, neonatal renal impairment.¹

Avoid use of NSAIAs in pregnant women at about ≥30 weeks’ gestation; if use required between about 20 and 30 weeks’ gestation, use lowest effective dosage and shortest possible duration of treatment.¹

Consider monitoring amniotic fluid volume via ultrasound examination if treatment duration >48 hours; if oligohydramnios occurs, discontinue drug and follow up according to clinical practice.¹

Hematologic Toxicity

Anemia reported.¹ May be due to occult or gross blood loss, fluid retention, or an incompletely described effect on erythropoiesis.¹ Determine hemoglobin concentration or hematocrit if signs or symptoms of anemia occur.¹

NSAIAs may increase the risk of bleeding.¹ Patients with certain coexisting conditions (e.g., coagulation disorders) or receiving concomitant therapy with anticoagulants, antiplatelet agents, SSRIs, or SNRIs may be at increased risk; monitor such patients for bleeding.¹

Masking of Inflammation and Fever

The possibility that the antipyretic and anti-inflammatory effects of flurbiprofen may mask the usual signs and symptoms of infection or other diseases should be considered.¹

Laboratory Monitoring

Obtain CBC and chemistry profile periodically during long-term use.¹

Ophthalmologic Effects

Visual disturbances (e.g., blurred and/or diminished vision) reported; ophthalmic evaluation recommended if visual changes occur.¹

Specific Populations

Pregnancy

Use of NSAIAs during pregnancy at about ≥30 weeks’ gestation can cause premature closure of the fetal ductus arteriosus; use at about ≥20 weeks’ gestation associated with fetal renal dysfunction resulting in oligohydramnios and, in some cases, neonatal renal impairment.¹

Avoid use of NSAIAs in pregnant women at about ≥30 weeks’ gestation; if use required between about 20 and 30 weeks’ gestation, use lowest effective dosage and shortest possible duration of treatment; consider monitoring amniotic fluid volume via ultrasound examination if treatment duration >48 hours; if oligohydramnios occurs, discontinue drug and follow up according to clinical practice.¹

Fetal renal dysfunction resulting in oligohydramnios and, in some cases, neonatal renal impairment observed, on average, following days to weeks of maternal NSAIA use; infrequently, oligohydramnios observed as early as 48 hours after initiation of NSAIAs.¹ Oligohydramnios is often, but not always, reversible (generally within 3–6 days) following NSAIA discontinuance.¹ Complications of prolonged oligohydramnios may include limb contracture and delayed lung maturation.¹ In limited number of cases, neonatal renal dysfunction (sometimes irreversible) occurred without oligohydramnios.¹ Some neonates have required invasive procedures (e.g., exchange transfusion, dialysis).¹ Deaths associated with neonatal renal failure also reported.¹ Limitations of available data preclude a reliable estimate of the risk of adverse fetal and neonatal outcomes with maternal NSAIA use.¹ Available data on neonatal outcomes generally involved preterm infants; extent to which risks can be generalized to full-term infants is uncertain.¹

No adequate and well-controlled studies of flurbiprofen in pregnant women.¹ Embryofetal lethality, delayed parturition, prolonged labor, stillborn fetuses, and the presence of retained fetuses at necropsy observed in animal studies; no evidence of malformations.¹

Effects of flurbiprofen on labor and delivery not known. In studies in rats, NSAIAs delayed parturition and increased stillbirths.¹

Lactation

Distributed in small amounts into human milk.^{1 13 15} Consider developmental and health benefits of breast-feeding along with mother's clinical need for flurbiprofen and any potential adverse effects on the breast-fed infant from the drug or underlying maternal condition.¹

Females and Males of Reproductive Potential

NSAIAs may be associated with reversible infertility in some women.¹ Reversible delays in ovulation observed in limited studies in women receiving NSAIAs; animal studies indicate that inhibitors of prostaglandin synthesis can disrupt prostaglandin-mediated follicular rupture required for ovulation.¹

Consider withdrawal of NSAIAs in women experiencing difficulty conceiving or undergoing evaluation of infertility.¹

Pediatric Use

Safety and efficacy not established.¹

Geriatric Use

Geriatric patients may experience an increased incidence of adverse GI effects and are at greater risk of developing renal decompensation with NSAIAs.¹ Use with caution and at the lowest effective dosage for shortest possible duration.¹

Renal Impairment

Use not recommended in patients with severe renal impairment; however, If flurbiprofen must be used, closely monitor renal function.¹

Pharmacogenomic Considerations

CYP2C9 poor metabolizers: Flurbiprofen metabolism may be decreased substantially, half-life may be prolonged, and higher plasma concentrations of the drug may increase likelihood and/or severity of adverse effects.⁵²⁰

CYP2C9 intermediate metabolizers: Flurbiprofen metabolism may be moderately or mildly reduced in those with an AS of 1 or 1.5, respectively.⁵²⁰ Higher plasma flurbiprofen concentrations in intermediate metabolizers with an AS of 1 may increase likelihood of adverse effects.⁵²⁰ Presence of other factors affecting flurbiprofen clearance (e.g., hepatic impairment, advanced age) also may increase risk of adverse effects in intermediate metabolizers.⁵²⁰

Dosage reduction may be required based on CYP2C9 phenotype.⁵²⁰

Consult Clinical Pharmacogenetics Implementation Consortium Guideline (CPIC) for CYP2C9 and Nonsteroidal Anti-Inflammatory Drugs for additional information on interpretation of CYP2C9 genotype testing.⁵²⁰

Common Adverse Effects

Most common adverse effects (>3%): abdominal pain, dyspepsia, nausea, diarrhea, constipation, headache, edema, signs and symptoms of urinary tract infection.¹

Drug Interactions

Specific Drugs

Flurbiprofen Pharmacokinetics

Absorption

Bioavailability

Rapidly and almost completely absorbed following oral administration.^{1 2 3 13 14} Peak plasma concentrations usually attained within 1.5–3 hours.^{1 2}

Food

Food may alter rate but not extent of absorption.^{1 3 13}

Distribution

Extent

Distributed into human milk in very small amounts.^{1 13 15}

Plasma Protein Binding

>99% (principally albumin).^{1 2 13 14}

Elimination

Metabolism

Extensively metabolized.^{1 2 13 14} CYP2C9 plays an important role in the metabolism of flurbiprofen to its major metabolite, 4′-hydroxyflurbiprofen, which has weak anti-inflammatory activity.^{1 2 11}

Elimination Route

Following oral dosing, approximately 70% of the flurbiprofen dose is eliminated in urine as parent drug and metabolites, with <3% excreted as unchanged drug.^{1 3}

Half-life

Approximately 4.7 and 5.7 hours for R- and S-flurbiprofen, respectively.¹

Special Populations

In patients with renal impairment, clearance of metabolites may be decreased.¹

Stability

Storage

Oral

Tablets

20–25°C.¹

Actions

• Inhibits cyclooxygenase-1 (COX-1) and COX-2.²

• Pharmacologic actions similar to those of other prototypical NSAIAs; exhibits anti-inflammatory, analgesic, and antipyretic activity.^{1 2 3 6 7}

Advice to Patients

• Inform patients to read the medication guide that is provided each time flurbiprofen is dispensed.¹

• Risk of serious cardiovascular events (e.g., MI, stroke).¹ Advise patients to be alert for symptoms including chest pain, shortness of breath, weakness, or slurring of speech, and to report any of these symptoms to their clinician.¹

• Risk of GI bleeding and ulceration.¹ Advise patients to report symptoms of ulcerations and bleeding, including epigastric pain, dyspepsia, melena, and hematemesis to their clinician.¹

• Risk of anaphylactic reactions.¹ Inform patients of the signs of an anaphylactic reaction (e.g., difficulty breathing, swelling of the face or throat) and instruct patients to seek emergency medical care if these occur.¹

• Risk of serious skin reactions, including DRESS.¹ Advise patients to stop taking flurbiprofen and contact their clinician as soon as possible if a serious skin reaction develops.¹

• Risk of hepatotoxicity.¹ Stress importance of discontinuing therapy and contacting clinician immediately if signs and symptoms of hepatotoxicity (e.g., nausea, fatigue, lethargy, pruritus, jaundice, upper right quadrant tenderness, flu-like symptoms) occur.¹

• Risk of heart failure or edema; stress importance of reporting difficulty breathing, unexplained weight gain, or edema.¹

• Advise patients to inform clinicians if they are or plan to become pregnant or plan to breast-feed.¹

• Stress importance of avoiding NSAIA use beginning at 20 weeks’ gestation unless otherwise advised by a clinician; avoid NSAIAs beginning at 30 weeks’ gestation because of risk of premature closure of the fetal ductus arteriosus; monitoring for oligohydramnios may be necessary if NSAIA therapy required for >48 hours’ duration between about 20 and 30 weeks’ gestation.¹

• Stress importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs.¹

• Inform patients of other important precautionary information.¹

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

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